Selection on haemagglutinin imposes a bottleneck during mammalian transmission of reassortant H5N1 influenza viruses

Nat Commun. 2013:4:2636. doi: 10.1038/ncomms3636.

Abstract

The emergence of human-transmissible H5N1 avian influenza viruses poses a major pandemic threat. H5N1 viruses are thought to be highly genetically diverse both among and within hosts; however, the effects of this diversity on viral replication and transmission are poorly understood. Here we use deep sequencing to investigate the impact of within-host viral variation on adaptation and transmission of H5N1 viruses in ferrets. We show that, although within-host genetic diversity in haemagglutinin (HA) increases during replication in inoculated ferrets, HA diversity is dramatically reduced upon respiratory droplet transmission, in which infection is established by only 1-2 distinct HA segments from a diverse source virus population in transmitting animals. Moreover, minor HA variants present in as little as 5.9% of viruses within the source animal become dominant in ferrets infected via respiratory droplets. These findings demonstrate that selective pressures acting during influenza virus transmission among mammals impose a significant bottleneck.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptation, Biological
  • Animals
  • Ferrets / virology*
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • High-Throughput Nucleotide Sequencing
  • Host Specificity
  • Host-Pathogen Interactions
  • Humans
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Orthomyxoviridae Infections / transmission*
  • Orthomyxoviridae Infections / veterinary*
  • Orthomyxoviridae Infections / virology
  • Polymorphism, Single Nucleotide
  • Reassortant Viruses / genetics*
  • Selection, Genetic*
  • Species Specificity

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus